DNA Defect May Be Linked to Ovarian, Breast Cancer Risk

Researchers think they have found a new way to identify women at high risk for breast and ovarian cancer -- by checking for unstable DNA in their ovary cells.

The researchers concluded such a test could be a useful screen after finding that women with a strong family history of breast or ovarian cancer tend to inherit a defect that impairs DNA repair.

The genetic defect leads to low levels of a protein that repairs DNA in ovary cells – and such ovary cells tend to have broken chromosomes.

It's not yet clear exactly why the defect leads to breast and ovarian cancer, note Oregon Health & Science University researchers Tanja Pejovic, MD, PhD, and colleagues.

But testing ovary cells for susceptibility to chromosome breakage would tell women with family histories of these cancers whether they should consider preventive measures, such as mastectomy or removal of their ovaries.

"Once this method is fully developed, we will be able to tell a young woman who has a family history of ovarian or breast cancer, but who wants to have children, whether she is at risk or not, without removing her ovary," Pejovic said in a news release.

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BRCA1 and BRCA2 Not the Whole Story

Current genetic testing can tell a woman whether she carries the BRCA1 or BRCA2 genes linked to breast and ovarian cancer.

But not all women who inherit breast or ovarian cancer risk carry those genes.

In the newly reported study, Pejovic's team examined ovary cells from three groups of women who had their ovaries removed.

One group of eight women had ovarian cancer. A second group of six women came from families at high risk of ovarian cancer, and were having their ovaries removed as a preventive measure.

The third group had no cancer or family history of cancer, but had other gynecologic diseases.

The researchers found that ovary cells from five of the high-risk women, and from three of the women with ovarian cancer, were highly susceptible to a chemical that damages DNA.

And five of these eight women with susceptible ovary cells had low levels of the DNA-repair protein called FANCD2.

"We have discovered that, by testing ovarian cells for chromosome breakage, we may be able to identify many more women at risk for ovarian and breast cancer than by using BRCA1 and BRCA2 mutation testing," Pejovic said. "We are also suggesting that low levels of FANCD2 protein are associated with this increased chromosome breakage."

While the women in the study had their ovaries removed, Pejovic says any future testing would use minimally invasive surgery to scrape just a few cells from a woman's ovary.

The findings appear in the Sept. 15 issue of the journal Cancer Research.

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By Daniel J. DeNoon, reviewed by Louise Chang, MD

SOURCES: Pejovic, T. Cancer Research, Sept. 15, 2006; vol 66: manuscript received ahead of publication. News release, Oregon Health & Science University, Portland.